The electrical membrane potential is an important property for the functioning of living cells. Temporal variations of this potential generated by synaptic interactions and expressed as nerve ...
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The electrical membrane potential is an important property for the functioning of living cells. Temporal variations of this potential generated by synaptic interactions and expressed as nerve impulses are central for signaling within nervous systems. Because neuronal signaling has this electrical basis, electrophysiology underlies neurophysiology. The primary objective of the NeuroDynamix II text is to provide a deep introduction to neurophysiology. The approach is to introduce the elements of electrical circuits, batteries, resistors and capacitors, and to build on that foundation to reconstruct the parallel conductance model that Hodgkin and Huxley employed for resting potentials and nerve impulses. The text presents brief historical sketches of, and introduces students to the fundamental concepts of neurophysiology. Following each didactic presentation, modeling exercises-hands-on simulations-serve to deepen the reader's understanding of basic neurophysiological techniques, including intracellular recording and voltage-clamp recording. The computer models present experimental results dynamically; that is, results are displayed as they are generated, providing a sense of experimental verisimilitude. NeuroDynamix II embodies a tight interdependence between the didactic text and the free, online NDX II software. Section I provides explicit, illustrated introductions to electrical concepts, the properties of ion channels, resting and action potentials, synaptic interactions, and neuronal circuits. Each didactic chapter concludes with detailed “Lessons” that preconfigure NDX II models to illustrate and explore neurophysiological principles. Section II provides brief descriptions of seven integrated models, with complete glossaries of variable and parameter names and units. Section III presents a detailed description of the equations for each computer simulation, whereas Section IV summarizes numerical methods for solving the differential equations. The text concludes with a brief guide for accessing the online NDX II modeling program and a bibliography.Less

W. Otto FriesenJonathon Friesen

Published in print: 2009-12-01

The electrical membrane potential is an important property for the functioning of living cells. Temporal variations of this potential generated by synaptic interactions and expressed as nerve impulses are central for signaling within nervous systems. Because neuronal signaling has this electrical basis, electrophysiology underlies neurophysiology. The primary objective of the NeuroDynamix II text is to provide a deep introduction to neurophysiology. The approach is to introduce the elements of electrical circuits, batteries, resistors and capacitors, and to build on that foundation to reconstruct the parallel conductance model that Hodgkin and Huxley employed for resting potentials and nerve impulses. The text presents brief historical sketches of, and introduces students to the fundamental concepts of neurophysiology. Following each didactic presentation, modeling exercises-hands-on simulations-serve to deepen the reader's understanding of basic neurophysiological techniques, including intracellular recording and voltage-clamp recording. The computer models present experimental results dynamically; that is, results are displayed as they are generated, providing a sense of experimental verisimilitude. NeuroDynamix II embodies a tight interdependence between the didactic text and the free, online NDX II software. Section I provides explicit, illustrated introductions to electrical concepts, the properties of ion channels, resting and action potentials, synaptic interactions, and neuronal circuits. Each didactic chapter concludes with detailed “Lessons” that preconfigure NDX II models to illustrate and explore neurophysiological principles. Section II provides brief descriptions of seven integrated models, with complete glossaries of variable and parameter names and units. Section III presents a detailed description of the equations for each computer simulation, whereas Section IV summarizes numerical methods for solving the differential equations. The text concludes with a brief guide for accessing the online NDX II modeling program and a bibliography.

The Axon model simulates the equations and parameters derived from experiments by Hodgkin and Huxley on the squid giant axon. Because of the exact correspondence between the equations incorporated ...
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The Axon model simulates the equations and parameters derived from experiments by Hodgkin and Huxley on the squid giant axon. Because of the exact correspondence between the equations incorporated into this model and the equations developed in the studies of Hodgkin and Huxley, this model generates graphs that mirror precisely the theoretical curves depicted in the Hodgkin-Huxley papers on the squid axon. Three similar models are included in this chapter: the single space-clamped axon, simultaneous simulations of several spaced-clamped axons to compare model output when parameters are altered, and a simulation of the spatially extended axon to illustrate impulse propagation.Less

Axon Models

W. Otto FriesenJonathon A. Friesen

Published in print: 2009-12-01

The Axon model simulates the equations and parameters derived from experiments by Hodgkin and Huxley on the squid giant axon. Because of the exact correspondence between the equations incorporated into this model and the equations developed in the studies of Hodgkin and Huxley, this model generates graphs that mirror precisely the theoretical curves depicted in the Hodgkin-Huxley papers on the squid axon. Three similar models are included in this chapter: the single space-clamped axon, simultaneous simulations of several spaced-clamped axons to compare model output when parameters are altered, and a simulation of the spatially extended axon to illustrate impulse propagation.

The Patch model illustrates results obtained from patch-clamp experiments. This chapter describes the elementary equations for currents through individual ion channels, based on Ohm's law. Because ...
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The Patch model illustrates results obtained from patch-clamp experiments. This chapter describes the elementary equations for currents through individual ion channels, based on Ohm's law. Because there are no time-dependent variables, no numerical integration is required.Less

Equations Underlying the Patch Model

W. Otto FriesenJonathon A. Friesen

Published in print: 2009-12-01

The Patch model illustrates results obtained from patch-clamp experiments. This chapter describes the elementary equations for currents through individual ion channels, based on Ohm's law. Because there are no time-dependent variables, no numerical integration is required.

The Axon models present the fundamental concepts that underlie the generation and propagation of the nerve impulses. This chapter includes a complete list of the equations that describe the ...
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The Axon models present the fundamental concepts that underlie the generation and propagation of the nerve impulses. This chapter includes a complete list of the equations that describe the Hodgkin-Huxley parallel conductance model specifically for squid axons, but these equations can be used to simulate nearly any action potential. The various currents generated by ionic conductances are individually described by their own equations. Ionic currents are controlled by membrane conductances and the appropriate electrochemical driving forces.Less

Equations Underlying the Axon Models

W. Otto FriesenJonathon A. Friesen

Published in print: 2009-12-01

The Axon models present the fundamental concepts that underlie the generation and propagation of the nerve impulses. This chapter includes a complete list of the equations that describe the Hodgkin-Huxley parallel conductance model specifically for squid axons, but these equations can be used to simulate nearly any action potential. The various currents generated by ionic conductances are individually described by their own equations. Ionic currents are controlled by membrane conductances and the appropriate electrochemical driving forces.

The Patch model simulates the dynamics of a small piece of cell membrane as observed with the patch-clamp technique. Either individual channels in a small patch of membrane or the macroscopic current ...
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The Patch model simulates the dynamics of a small piece of cell membrane as observed with the patch-clamp technique. Either individual channels in a small patch of membrane or the macroscopic current observed with the whole cell patch clamp may be simulated. Channels are viewed as all-or-none conductances that are gated by voltage (sodium and potassium channels), by a messenger ligand (ACh channel), or not gated (chloride channel). The experimenter can specify the channel type and the number of channels found in the membrane patch. Properties that are simulated include the random opening of channels, the gating of the channels by membrane potential, the voltage dependence of the currents through the channels, the dependence of single channel currents on channel conductance, and the summation of microscopic currents from many individual, randomly gated channels to yield a noisy macroscopic current.Less

Patch Model

W. Otto FriesenJonathon A. Friesen

Published in print: 2009-12-01

The Patch model simulates the dynamics of a small piece of cell membrane as observed with the patch-clamp technique. Either individual channels in a small patch of membrane or the macroscopic current observed with the whole cell patch clamp may be simulated. Channels are viewed as all-or-none conductances that are gated by voltage (sodium and potassium channels), by a messenger ligand (ACh channel), or not gated (chloride channel). The experimenter can specify the channel type and the number of channels found in the membrane patch. Properties that are simulated include the random opening of channels, the gating of the channels by membrane potential, the voltage dependence of the currents through the channels, the dependence of single channel currents on channel conductance, and the summation of microscopic currents from many individual, randomly gated channels to yield a noisy macroscopic current.

The Shortt clock, made in the 1920s, is the most famous accurate clock pendulum ever known, having an accuracy of one second per year when kept at nearly constant temperature. Almost all of a ...
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The Shortt clock, made in the 1920s, is the most famous accurate clock pendulum ever known, having an accuracy of one second per year when kept at nearly constant temperature. Almost all of a pendulum clock's accuracy resides in its pendulum. If the pendulum is accurate, the clock will be accurate. This book describes many scientific aspects of pendulum design and operation in simple terms with experimental data, and little mathematics. It has been written, looking at all the different parts and aspects of the pendulum in great detail, chapter by chapter, reflecting the degree of attention necessary for making a pendulum run accurately. The topics covered include the dimensional stability of different pendulum materials, good and poor suspension spring designs, the design of mechanical joints and clamps, effect of quartz on accuracy, temperature compensation, air drag of different bob shapes and making a sinusoidal electromagnetic drive. One whole chapter is devoted to simple ways of improving the accuracy of ordinary low-cost pendulum clocks, which have a different construction compared to the more expensive designs of substantially well-made ones. This book will prove invaluable to anyone who wants to know how to make a more accurate pendulum or pendulum clock.Less

Accurate Clock Pendulums

Robert J. Matthys

Published in print: 2004-06-03

The Shortt clock, made in the 1920s, is the most famous accurate clock pendulum ever known, having an accuracy of one second per year when kept at nearly constant temperature. Almost all of a pendulum clock's accuracy resides in its pendulum. If the pendulum is accurate, the clock will be accurate. This book describes many scientific aspects of pendulum design and operation in simple terms with experimental data, and little mathematics. It has been written, looking at all the different parts and aspects of the pendulum in great detail, chapter by chapter, reflecting the degree of attention necessary for making a pendulum run accurately. The topics covered include the dimensional stability of different pendulum materials, good and poor suspension spring designs, the design of mechanical joints and clamps, effect of quartz on accuracy, temperature compensation, air drag of different bob shapes and making a sinusoidal electromagnetic drive. One whole chapter is devoted to simple ways of improving the accuracy of ordinary low-cost pendulum clocks, which have a different construction compared to the more expensive designs of substantially well-made ones. This book will prove invaluable to anyone who wants to know how to make a more accurate pendulum or pendulum clock.

The rapid conduction of signals by neurons over distances greater than about 1 mm occurs almost exclusively by electrical impulses. This chapter presents the fundamental concepts that underlie the ...
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The rapid conduction of signals by neurons over distances greater than about 1 mm occurs almost exclusively by electrical impulses. This chapter presents the fundamental concepts that underlie the generation and propagation of these nerve impulses. After a brief historical summary, the remainder of the chapter describes the voltage-clamp experiments of A. L. Hodgkin and A. F. Huxley on the giant axon of the squid. The results and the conclusions furnished by these seminal experiments provide the bases for the current understanding of the electrical nature of neuronal signaling. The Hodgkin-Huxley experiments, together with the equations that encapsulate the experimental results, are presented here in detail to emphasize their central importance for neurophysiology and to present an exemplar of science at its best.Less

Basis of the Nerve Impulse

W. Otto FriesenJonathon A. Friesen

Published in print: 2009-12-01

The rapid conduction of signals by neurons over distances greater than about 1 mm occurs almost exclusively by electrical impulses. This chapter presents the fundamental concepts that underlie the generation and propagation of these nerve impulses. After a brief historical summary, the remainder of the chapter describes the voltage-clamp experiments of A. L. Hodgkin and A. F. Huxley on the giant axon of the squid. The results and the conclusions furnished by these seminal experiments provide the bases for the current understanding of the electrical nature of neuronal signaling. The Hodgkin-Huxley experiments, together with the equations that encapsulate the experimental results, are presented here in detail to emphasize their central importance for neurophysiology and to present an exemplar of science at its best.

In the cerebral cortex of awake animals, neurons are subject to tremendous fluctuating activity, mostly of synaptic origin, termed “synaptic noise”. Synaptic noise is the dominant source of membrane ...
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In the cerebral cortex of awake animals, neurons are subject to tremendous fluctuating activity, mostly of synaptic origin, termed “synaptic noise”. Synaptic noise is the dominant source of membrane potential fluctuations in neurons and can have a strong influence on their integrative properties. We review here the experimental measurements of synaptic noise, and its modelling by conductance-based stochastic processes. We then review the consequences of synaptic noise on neuronal integrative properties, as predicted by computational models and investigated experimentally using the dynamic clamp. We also review analysis methods such as spike-triggered average or conductance analysis, which are derived from the modelling of synaptic noise by stochastic processes. These different approaches aim at understanding the integrative properties of neocortical neurons in the intact brain.Less

Alain DestexheMichelle Rudolph-Lilith

Published in print: 2009-09-01

In the cerebral cortex of awake animals, neurons are subject to tremendous fluctuating activity, mostly of synaptic origin, termed “synaptic noise”. Synaptic noise is the dominant source of membrane potential fluctuations in neurons and can have a strong influence on their integrative properties. We review here the experimental measurements of synaptic noise, and its modelling by conductance-based stochastic processes. We then review the consequences of synaptic noise on neuronal integrative properties, as predicted by computational models and investigated experimentally using the dynamic clamp. We also review analysis methods such as spike-triggered average or conductance analysis, which are derived from the modelling of synaptic noise by stochastic processes. These different approaches aim at understanding the integrative properties of neocortical neurons in the intact brain.

Invented by Bert Sakmann and Erwin Neher during the 1970s, the patch-clamp recording technique aids scientists in examining the functions of individual protein molecules that form ion channels in ...
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Invented by Bert Sakmann and Erwin Neher during the 1970s, the patch-clamp recording technique aids scientists in examining the functions of individual protein molecules that form ion channels in cell membranes. The importance of this outstanding contribution, which has revolutionized neurophysiology and greatly augmented understanding of cell membranes, is underscored by the fact that Sakmann and Neher received the Nobel Prize in 1991. The fundamental finding arising from patch-clamp experiments is that currents through cell membranes pass through protein channels. This chapter provides a brief introduction to the patch-clamp technique and presents the fundamental equations that govern currents through individual ion channels. The electrophysiology of three types of ion channels is described: nongated chloride channels, voltage-gated sodium and potassium channels, and ligand-gated acetylcholine channels.Less

Patch-Clamp Recording

W. Otto FriesenJonathon A. Friesen

Published in print: 2009-12-01

Invented by Bert Sakmann and Erwin Neher during the 1970s, the patch-clamp recording technique aids scientists in examining the functions of individual protein molecules that form ion channels in cell membranes. The importance of this outstanding contribution, which has revolutionized neurophysiology and greatly augmented understanding of cell membranes, is underscored by the fact that Sakmann and Neher received the Nobel Prize in 1991. The fundamental finding arising from patch-clamp experiments is that currents through cell membranes pass through protein channels. This chapter provides a brief introduction to the patch-clamp technique and presents the fundamental equations that govern currents through individual ion channels. The electrophysiology of three types of ion channels is described: nongated chloride channels, voltage-gated sodium and potassium channels, and ligand-gated acetylcholine channels.

This chapter describes macroscopic membrane currents measured in amphibian and mammalian nodes of Ranvier with the voltage-clamp method. These results are compared with those of single-channel ...
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This chapter describes macroscopic membrane currents measured in amphibian and mammalian nodes of Ranvier with the voltage-clamp method. These results are compared with those of single-channel recordings, which provide important data on channel characteristics in myelinated axons. The results obtained from the calculation of the action potentials with voltage-clamp data obtained from frog, rat, and human nerve fibers are also reviewed. It is shown that the properties of the various new ionic channel types detected with the patch-clamp technique help explain previously unsolved problems concerning the ionic basis of accommodation, resting potential, and various pathophysiological phenomena.Less

WERNER VOGELJÜRGEN R. SCHWARZ

Published in print: 1995-05-25

This chapter describes macroscopic membrane currents measured in amphibian and mammalian nodes of Ranvier with the voltage-clamp method. These results are compared with those of single-channel recordings, which provide important data on channel characteristics in myelinated axons. The results obtained from the calculation of the action potentials with voltage-clamp data obtained from frog, rat, and human nerve fibers are also reviewed. It is shown that the properties of the various new ionic channel types detected with the patch-clamp technique help explain previously unsolved problems concerning the ionic basis of accommodation, resting potential, and various pathophysiological phenomena.

This chapter focuses on various electrophysiological techniques. The voltage-clamp technique has been a powerful tool in the development of membrane biophysics. Applied to large cells, such as squid ...
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This chapter focuses on various electrophysiological techniques. The voltage-clamp technique has been a powerful tool in the development of membrane biophysics. Applied to large cells, such as squid axons or giant snail neurones, this technique allows for the reconstruction of an action potential by means of separate Na+ and K+ conductances. However, the need to penetrate cells with two micro-electrodes restricts its use only to large cells. This limitation can be partly overcome by the introduction of a voltage-clamp circuit, which only needs one micro-electrode; this has been useful for describing ion currents in small cells. At the same time, the patch-clamp technique for measuring single currents was developed by Neher and Sakmann (1976). When the improved patch-clamp technique for single-channel and whole-cell recordings was described in detail it quickly became the technique for investigating the electrical properties of cell membranes. This method represents a major advance in the ability to monitor cell membrane function.Less

Electrophysiological techniques

Jean Mironneau

Published in print: 1998-01-22

This chapter focuses on various electrophysiological techniques. The voltage-clamp technique has been a powerful tool in the development of membrane biophysics. Applied to large cells, such as squid axons or giant snail neurones, this technique allows for the reconstruction of an action potential by means of separate Na+ and K+ conductances. However, the need to penetrate cells with two micro-electrodes restricts its use only to large cells. This limitation can be partly overcome by the introduction of a voltage-clamp circuit, which only needs one micro-electrode; this has been useful for describing ion currents in small cells. At the same time, the patch-clamp technique for measuring single currents was developed by Neher and Sakmann (1976). When the improved patch-clamp technique for single-channel and whole-cell recordings was described in detail it quickly became the technique for investigating the electrical properties of cell membranes. This method represents a major advance in the ability to monitor cell membrane function.

The nerve impulse is the basis of all human thoughts and emotions, and of all sensations and movements. As such, it has been the subject of scientific enquiry for more than two centuries, beginning ...
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The nerve impulse is the basis of all human thoughts and emotions, and of all sensations and movements. As such, it has been the subject of scientific enquiry for more than two centuries, beginning with Galvani’s chance observation that a frog’s leg twitched in response to an electrostatic discharge nearby. From being a metaphysical concept, the impulse became a phenomenon that could be recorded and have its velocity determined. However, the nature of the brief permeability changes in the nerve membrane that made the impulse possible, and of the way in which the nerve endings influenced the excitability of connecting neurons, remained problems that taxed the ingenuity of physiologists for many years. An important breakthrough was the discovery of giant nerve fibres in the squid, fibres large enough for new techniques to be employed, as in the voltage-clamp experiments of Hodgkin and Huxley immediately after World War II. The story culminates with the recent discovery of the 3-dimensional structure and detailed functioning of the ion channels, following MacKinnon’s X-ray diffraction studies, and with the revelation that a host of clinical disorders result from malfunction of the ion channels.Less

Galvani’s Spark : The Story of the Nerve Impulse

Alan McComas

Published in print: 2011-08-08

The nerve impulse is the basis of all human thoughts and emotions, and of all sensations and movements. As such, it has been the subject of scientific enquiry for more than two centuries, beginning with Galvani’s chance observation that a frog’s leg twitched in response to an electrostatic discharge nearby. From being a metaphysical concept, the impulse became a phenomenon that could be recorded and have its velocity determined. However, the nature of the brief permeability changes in the nerve membrane that made the impulse possible, and of the way in which the nerve endings influenced the excitability of connecting neurons, remained problems that taxed the ingenuity of physiologists for many years. An important breakthrough was the discovery of giant nerve fibres in the squid, fibres large enough for new techniques to be employed, as in the voltage-clamp experiments of Hodgkin and Huxley immediately after World War II. The story culminates with the recent discovery of the 3-dimensional structure and detailed functioning of the ion channels, following MacKinnon’s X-ray diffraction studies, and with the revelation that a host of clinical disorders result from malfunction of the ion channels.

John Moore initially became known for elucidating the action of tetrodotoxin and other neurotoxins using his innovative sucrose gap method for voltage clamping squid axon. He also was a pioneer in ...
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John Moore initially became known for elucidating the action of tetrodotoxin and other neurotoxins using his innovative sucrose gap method for voltage clamping squid axon. He also was a pioneer in the nascent area of computational neuroscience, using computer simulations in parallel with experiments to predict experimental results and thus validate the concepts used in modeling. Intrigued by the possibility of applying his knowledge of physics to learn how neurons employ electricity to generate and transmit signals, he led the field in exploring how ion channels and neuronal morphology affect excitation and signal propagation. He developed electronic instrumentation of high precision for electrophysiology, the result of experience gained through an unconventional career path: early training in physics, assignments involving feedback in the Manhattan Project, and learning principles of operational amplifiers at the RCA Laboratories. His summers at the Marine Biological Laboratory in Woods Hole, MA, now exceeding 50, made much of his work possible and established the MBL as his intellectual home. In retirement, he developed the educational software Neurons In Action, coauthored with his wife Ann Stuart, that is now widely used as a learning tool in neurophysiology.Less

John Wilson Moore

Larry R. Squire

Published in print: 2011-09-09

John Moore initially became known for elucidating the action of tetrodotoxin and other neurotoxins using his innovative sucrose gap method for voltage clamping squid axon. He also was a pioneer in the nascent area of computational neuroscience, using computer simulations in parallel with experiments to predict experimental results and thus validate the concepts used in modeling. Intrigued by the possibility of applying his knowledge of physics to learn how neurons employ electricity to generate and transmit signals, he led the field in exploring how ion channels and neuronal morphology affect excitation and signal propagation. He developed electronic instrumentation of high precision for electrophysiology, the result of experience gained through an unconventional career path: early training in physics, assignments involving feedback in the Manhattan Project, and learning principles of operational amplifiers at the RCA Laboratories. His summers at the Marine Biological Laboratory in Woods Hole, MA, now exceeding 50, made much of his work possible and established the MBL as his intellectual home. In retirement, he developed the educational software Neurons In Action, coauthored with his wife Ann Stuart, that is now widely used as a learning tool in neurophysiology.

Nerve impulses traversing the brain were likened by Sherrington to points of light in an enchanted loom. The electrochemical nature of the nerve impulse was largely elucidated by Hodgkin and Huxley ...
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Nerve impulses traversing the brain were likened by Sherrington to points of light in an enchanted loom. The electrochemical nature of the nerve impulse was largely elucidated by Hodgkin and Huxley in their studies of the squid giant axon in the years immediately before and after the 1939–45 war. Although the impact of this work within the neuroscience community was immense, it was overshadowed elsewhere by the discovery of the helical structure of DNA by Watson and Crick at about the same time. Both types of work had involved complex mathematics and deep insights, but the Hodgkin-Huxley studies had included a series of brilliant experiments and had been the climax of almost two centuries of nerve impulse research.Less

Introduction

Alan J. McComas

Published in print: 2011-08-08

Nerve impulses traversing the brain were likened by Sherrington to points of light in an enchanted loom. The electrochemical nature of the nerve impulse was largely elucidated by Hodgkin and Huxley in their studies of the squid giant axon in the years immediately before and after the 1939–45 war. Although the impact of this work within the neuroscience community was immense, it was overshadowed elsewhere by the discovery of the helical structure of DNA by Watson and Crick at about the same time. Both types of work had involved complex mathematics and deep insights, but the Hodgkin-Huxley studies had included a series of brilliant experiments and had been the climax of almost two centuries of nerve impulse research.

Now in Chicago, Kenneth Cole employs a negative feedback circuit, devised by a colleague, to clamp the voltage across the membrane of the squid giant axon. He shows that during the action potential ...
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Now in Chicago, Kenneth Cole employs a negative feedback circuit, devised by a colleague, to clamp the voltage across the membrane of the squid giant axon. He shows that during the action potential there is an initial inward current followed by an outward current, and he attributes the latter to potassium ions. Hodgkin visits Cole who shows him the new technique and loans him some of the apparatus needed for voltage-clamp work. Within a few months Hodgkin has his own voltage-clamp system built and resumes work with Huxley on the squid giant axon at Plymouth, initially with Katz as well. By replacing sodium in the bathing fluid with choline, they are able to show that the early inward current during the action potential is indeed a sodium one, and that the later, outward, current is carried by potassium ions. On the basis of the experimental data Huxley is able to derive an equation describing the flow of current through the nerve membrane at any instant. He and Hodgkin introduce special terms which they interpret as the effects of mobile particles within the membrane. From their equations, Huxley is able to compute the form and conduction velocity of the action potential. The British voltage-clamp work is published in five papers and creates a stir; however, Cole’s assistance is not acknowledged. Hodgkin and Huxley share the 1963 Nobel Prize with Eccles.Less

The Voltage Clamp

Alan J. McComas

Published in print: 2011-08-08

Now in Chicago, Kenneth Cole employs a negative feedback circuit, devised by a colleague, to clamp the voltage across the membrane of the squid giant axon. He shows that during the action potential there is an initial inward current followed by an outward current, and he attributes the latter to potassium ions. Hodgkin visits Cole who shows him the new technique and loans him some of the apparatus needed for voltage-clamp work. Within a few months Hodgkin has his own voltage-clamp system built and resumes work with Huxley on the squid giant axon at Plymouth, initially with Katz as well. By replacing sodium in the bathing fluid with choline, they are able to show that the early inward current during the action potential is indeed a sodium one, and that the later, outward, current is carried by potassium ions. On the basis of the experimental data Huxley is able to derive an equation describing the flow of current through the nerve membrane at any instant. He and Hodgkin introduce special terms which they interpret as the effects of mobile particles within the membrane. From their equations, Huxley is able to compute the form and conduction velocity of the action potential. The British voltage-clamp work is published in five papers and creates a stir; however, Cole’s assistance is not acknowledged. Hodgkin and Huxley share the 1963 Nobel Prize with Eccles.

A “gating” current, predicted by the Hodgkin-Huxley equations twenty years earlier, is finally detected in the squid giant axon. Soon after, Bert Sakmann and Erwin Neher develop a patch clamp method ...
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A “gating” current, predicted by the Hodgkin-Huxley equations twenty years earlier, is finally detected in the squid giant axon. Soon after, Bert Sakmann and Erwin Neher develop a patch clamp method for recording the opening and closing of single ionic channels in a membrane. They apply their method to the acetylcholine receptor, while Shosaku Numa and his colleagues determine the amino acid sequence of the receptor by means of DNA analysis. Finally, the 3-dimensional outline of the acetylcholine receptor is derived by Nigel Unwin and Chikashi Toyoshima using X-ray diffraction and electron microscopy. Numa’s group turn their attention to the voltage-gated sodium channel and show that it is formed from four repeats of a basic unit, each of which has six membrane-spanning segments. Although the amino acids likely to form the “gates” are identified, the operating mechanism of the gates remains unknown.Less

The Single Ion Channel

Alan J. McComas

Published in print: 2011-08-08

A “gating” current, predicted by the Hodgkin-Huxley equations twenty years earlier, is finally detected in the squid giant axon. Soon after, Bert Sakmann and Erwin Neher develop a patch clamp method for recording the opening and closing of single ionic channels in a membrane. They apply their method to the acetylcholine receptor, while Shosaku Numa and his colleagues determine the amino acid sequence of the receptor by means of DNA analysis. Finally, the 3-dimensional outline of the acetylcholine receptor is derived by Nigel Unwin and Chikashi Toyoshima using X-ray diffraction and electron microscopy. Numa’s group turn their attention to the voltage-gated sodium channel and show that it is formed from four repeats of a basic unit, each of which has six membrane-spanning segments. Although the amino acids likely to form the “gates” are identified, the operating mechanism of the gates remains unknown.

This chapter discusses how to make solid one-piece type of pendulum suspension springs. There are three types of pendulum suspension springs: the mechanically clamped type, the soldered assembly ...
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This chapter discusses how to make solid one-piece type of pendulum suspension springs. There are three types of pendulum suspension springs: the mechanically clamped type, the soldered assembly type, and the solid one-piece type. The mechanically clamped type is the easiest to make, but its clock rate is variable and dependent on the clamping forces and clamping surfaces. A 10-microinch change in the length of a 1-second beat pendulum amounts to an error of 3.7 seconds per year. To meet the microinch length tolerance needed for an accurate pendulum clock, a mechanically bolted assembly must have microinch tolerances on the clamped surfaces, that is, an optical finish. Mechanically machined surfaces are not good enough, and introduce uncertainty as to where the spring ends and the end clamp actually begins. The uncertainty causes the pendulum's length and its timing to vary with temperature and the suspension spring's clamping pressure.Less

Solid one-piece suspension springs

Robert James Matthys

Published in print: 2004-06-03

This chapter discusses how to make solid one-piece type of pendulum suspension springs. There are three types of pendulum suspension springs: the mechanically clamped type, the soldered assembly type, and the solid one-piece type. The mechanically clamped type is the easiest to make, but its clock rate is variable and dependent on the clamping forces and clamping surfaces. A 10-microinch change in the length of a 1-second beat pendulum amounts to an error of 3.7 seconds per year. To meet the microinch length tolerance needed for an accurate pendulum clock, a mechanically bolted assembly must have microinch tolerances on the clamped surfaces, that is, an optical finish. Mechanically machined surfaces are not good enough, and introduce uncertainty as to where the spring ends and the end clamp actually begins. The uncertainty causes the pendulum's length and its timing to vary with temperature and the suspension spring's clamping pressure.

This chapter describes five different ways of fastening things to a quartz pendulum rod. To connect to a metal rod, a hole is drilled in it or a thread is cut on it. But how do you fasten something ...
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This chapter describes five different ways of fastening things to a quartz pendulum rod. To connect to a metal rod, a hole is drilled in it or a thread is cut on it. But how do you fasten something to quartz? Quartz is like glass it is brittle and breaks easily. Five types of fasteners are described here, with some pros and cons on each. The five fasteners are cemented sleeve, clamp ring, solder joint, dowel pin, and split sleeve. Any of the fasteners can be used at either the top or bottom of a quartz rod, for connecting to a suspension spring, bob, or rating nut. In most cases, the fastener material should be invar because of its low thermal expansion coefficient.Less

Fasteners for quartz pendulum rods

Robert James Matthys

Published in print: 2004-06-03

This chapter describes five different ways of fastening things to a quartz pendulum rod. To connect to a metal rod, a hole is drilled in it or a thread is cut on it. But how do you fasten something to quartz? Quartz is like glass it is brittle and breaks easily. Five types of fasteners are described here, with some pros and cons on each. The five fasteners are cemented sleeve, clamp ring, solder joint, dowel pin, and split sleeve. Any of the fasteners can be used at either the top or bottom of a quartz rod, for connecting to a suspension spring, bob, or rating nut. In most cases, the fastener material should be invar because of its low thermal expansion coefficient.

This chapter summarizes the progress in developing a model system for studying the control of neuronal Na channel distribution based on the squid giant axon and its cell bodies located in the giant ...
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This chapter summarizes the progress in developing a model system for studying the control of neuronal Na channel distribution based on the squid giant axon and its cell bodies located in the giant fibre lobe (GFL) of the stellate ganglion. Patch clamp methods have been employed to test the functional integrity of Na channels in GFL neurones maintained in primary culture, and to map the spatial distribution in cell bodies and axons. GFL neurones in vitro establish and maintain a strongly polarized Na channel distribution similar to that displayed by the system in vivo. Several manipulations that disrupt this cellular polarity, including a novel effect of the glycosylation inhibitor tunicamycin, have been identified. This drug appears to selectively inhibit high-level expression of Na channels in axonal membrane. Specificity of neuronal function at the cellular level is largely dictated by the precise spatial distribution of membrane receptors and channels. In general, the functional properties of many channels and receptors have been well studied, and in some cases their spatial distributions have been carefully mapped. Although this information is vital to understanding nerve cell function, there is still a need to learn much more about the cell biological dynamics that control both the properties and the spatial distributions of these important membrane proteins. All neurones are functionally and morphologically polarized, and the number of cellular control elements is large.Less

Control of the spatial distribution of sodium channels in the squid giant axon and its cell bodies

W. F. GillyM. T. LuceroM. PerriJ. Rosenthal

Published in print: 1995-04-27

This chapter summarizes the progress in developing a model system for studying the control of neuronal Na channel distribution based on the squid giant axon and its cell bodies located in the giant fibre lobe (GFL) of the stellate ganglion. Patch clamp methods have been employed to test the functional integrity of Na channels in GFL neurones maintained in primary culture, and to map the spatial distribution in cell bodies and axons. GFL neurones in vitro establish and maintain a strongly polarized Na channel distribution similar to that displayed by the system in vivo. Several manipulations that disrupt this cellular polarity, including a novel effect of the glycosylation inhibitor tunicamycin, have been identified. This drug appears to selectively inhibit high-level expression of Na channels in axonal membrane. Specificity of neuronal function at the cellular level is largely dictated by the precise spatial distribution of membrane receptors and channels. In general, the functional properties of many channels and receptors have been well studied, and in some cases their spatial distributions have been carefully mapped. Although this information is vital to understanding nerve cell function, there is still a need to learn much more about the cell biological dynamics that control both the properties and the spatial distributions of these important membrane proteins. All neurones are functionally and morphologically polarized, and the number of cellular control elements is large.

Schwann cells are the class of glial cells of the peripheral nervous system associated with axons. The myelin-forming Schwann cells of large-diameter vertebrate axons have a clear physiological ...
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Schwann cells are the class of glial cells of the peripheral nervous system associated with axons. The myelin-forming Schwann cells of large-diameter vertebrate axons have a clear physiological function important for axonal physiology. The squid giant axon shows a complex system for chemical signalling from axon to Schwann cell, which may be an important way for the Schwann cells to match their activity to the requirements of the axon. As the signalling involves modulation of the electrophysiological properties of the Schwann cell, a complete understanding of the signalling requires consideration of these electrical properties. The electrophysiological properties also determine the mechanisms available for ionic homeostasis of the periaxonal microenvironment. This chapter reviews current understanding of the resting and activated properties of the Schwann cell membrane, and the implications for signalling and ionic homeostasis. This survey of studies on the electrophysiology of squid Schwann cells shows a general consistency between observations in Sepioteuthis, Alloteuthis, and Loligo, good evidence for the generality of the phenomena. The documented membrane properties of the Schwann cells make for efficient periaxonal ion regulation. Further characterization of the membrane ion channels responsible for the resting and activated electrical behavior of the membranes requires rigorous study using the patch-clamp technique.Less

Electrophysiology of squid Schwann cells

N. Joan AbbottE. R. BrownY. PichonFumio Kukita

Published in print: 1995-04-27

Schwann cells are the class of glial cells of the peripheral nervous system associated with axons. The myelin-forming Schwann cells of large-diameter vertebrate axons have a clear physiological function important for axonal physiology. The squid giant axon shows a complex system for chemical signalling from axon to Schwann cell, which may be an important way for the Schwann cells to match their activity to the requirements of the axon. As the signalling involves modulation of the electrophysiological properties of the Schwann cell, a complete understanding of the signalling requires consideration of these electrical properties. The electrophysiological properties also determine the mechanisms available for ionic homeostasis of the periaxonal microenvironment. This chapter reviews current understanding of the resting and activated properties of the Schwann cell membrane, and the implications for signalling and ionic homeostasis. This survey of studies on the electrophysiology of squid Schwann cells shows a general consistency between observations in Sepioteuthis, Alloteuthis, and Loligo, good evidence for the generality of the phenomena. The documented membrane properties of the Schwann cells make for efficient periaxonal ion regulation. Further characterization of the membrane ion channels responsible for the resting and activated electrical behavior of the membranes requires rigorous study using the patch-clamp technique.